The global health crisis caused by HIV, the causative agent of Acquired Immunodeficiency Syndrome (AIDS), is unquestioned, and while recent advances in drug therapies have been successful in slowing the progression of AIDS, there is still a need to find a safer, more efficient, less expensive way to control the virus.
HIV typically establishes an infection by first attaching to CD4 receptors on white blood cells and then grabbing a second receptor known as CC Chemokine Receptor 5 (“CCR5”), which normally responds to immune chemicals called chemokines. Epidemiological and viral transmission studies have shown that viruses using the CCR5 receptor are often associated with transmission of HIV infection between individuals. Therefore, blocking these viruses by prophylactic treatment with a specific CCR5 inhibitor should prove an effective way to prevent HIV transmission in a susceptible population. For example, M. Lederman et al., Prevention of Vaginal SHIV Transmission in Rhesus Macaques Through Inhibition of CCR5, SCIENCE 306, 485-487 (Oct. 15, 2004), describe a study of the ability of Nα-(n-nonanoyl)-des-Ser1-[L-thioproline2, L-α-cyclohexyl-glycine3]RANTES (“PSC-RANTES”) to prevent acquisition of SHIV infection at a mucosal skin. Q. Hu et al., Blockade of Attachment and Fusion Receptors Inhibits HIV-1 Infection of Human Cervical Tissue, 199(8) J. EXP. MED. 1065-1075 (Apr. 19, 2004), describe the blockade of the effect of both CCR5 and CXCR4 to prevent infection.
The present invention relates to small molecules that are CCR5 antagonists, in particular, Compound A, (4,6-dimethylpyrimidin-5-yl)(4-((3 S)-4-((1R)-2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-methylpiperazin-1-yl)-4-methylpiperidin-1-yl)methanone, or a pharmaceutically salt thereof, which is disclosed in Baroudy et al., U.S. Pat. No. 6,391,865, incorporated herein by reference.

U.S. Pat. No. 6,391,865 discloses novel antagonists of the CCR5 receptor that are useful for the treatment of AIDS and related HIV infections, including Compound A. CCR5 receptors have also been reported to mediate cell transfer in inflammatory diseases such as arthritis, rheumatoid arthritis, atopic dermatitis, psoriasis, asthma and allergies, and inhibitors of such receptors are expected to be useful in the treatment of such diseases, and in the treatment of other inflammatory diseases or conditions such as inflammatory bowel disease, multiple sclerosis, solid organ transplant rejection and graft v. host disease.
Different forms—amorphous, solvate, and crystalline—of CCR5 antagonist compounds can provide different properties of stability, solubility, dissolution rate, hardness, compressibility and melting point, as well as other physical and mechanical properties. Such physical and mechanical properties can affect the ease of manufacture, formulation, storage and transport of the CCR5 antagonist compounds. Thus, there is a need for identification of new forms of CCR5 antagonist compounds and ways for preparing such forms.